Effects of β-adrenergic receptor on survival and inflammatory response of septic mice

Background The beta-adrenergic receptor (Beta-AR), associated with the treatment of cardiovascular and immune diseases, may constitute a novel therapeutic target for sepsis management.

Objective To breed some beta-receptor gene knockout mice (β-KO mice) and establish a cecal ligation and puncture (CLP) model, and evaluate the murine survival rates, organ pathology alterations, and inflammatory injury changes of mice.

Methods Upon genetic identification of β-KO mice, 12 male β-KO mice and an equivalent cohort of twelve wild-type (WT) mice under identical conditions were subjected to CLP, followed by a seven-day survival rate monitoring. Similarly, an additional set of 12 β-KO and 12 WT mice were selected, and hepatic and pulmonary tissues were harvested at 48 hours after CLP to observe histopathological changes. Immunohistochemical staining techniques were employed to detect alterations in tumor necrosis factor-alpha (TNF-α) and CD68 levels within hepatic and pulmonary tissues. Furthermore, enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the expression levels of hepatic tissue homogenate cytokines TNF-α and interleukin-6 (IL-6).

Results Genotypic identification confirmed successful breeding of β-KO mice, with a significant enhancement in seven-day survival rates in β-KO mice compared to the WT group (P=0.043). At 48 hours after CLP, β-KO mice exhibited amelioration in hepatic and pulmonary pathological injury scores relative to the WT group (P=0.022, P=0.006). Immunohistochemical staining revealed reduced levels of TNF-α and CD68 in the hepatic and pulmonary tissues of β-KO mice compared to WT. ELISA analyses demonstrated that the concentrations of pro-inflammatory cytokines TNF-α and IL-6 in the hepatic homogenates of β-KO mice were significantly lower than those in the WT group (P=0.009, P=0.022).

Conclusion Inhibition of beta-adrenergic signaling pathways enhances survival rates in septic mice, mitigates hepatic and pulmonary injury, and attenuates the expression of inflammatory cytokines, potentially exerting a protective effect in septic murine models.